Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: A cross-sectional study

Hilary P. Blumberg*, John H. Krystal, Ravi Bansal, Andrés Martin, James Dziura, Kathleen Durkin, Laura Martin, Elizabeth Gerard, Dennis S. Charney, Bradley S. Peterson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Background: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. Methods: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. Results: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. Conclusions: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.

Original languageEnglish (US)
Pages (from-to)611-618
Number of pages8
JournalBiological psychiatry
Issue number7
StatePublished - Apr 1 2006


  • Adolescent
  • Adult
  • Bipolar disorder
  • Magnetic resonance imaging
  • Prefrontal cortex

ASJC Scopus subject areas

  • Biological Psychiatry


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